MiR-146a functions as a potential tumor suppressor in retinoblastoma by negatively regulate neuro-oncological ventral antigen-1

Kaohsiung J Med Sci. 2021 Apr;37(4):286-293. doi: 10.1002/kjm2.12337. Epub 2020 Dec 19.

Abstract

MicroRNAs (miRNAs) are dysregulated in many tumors and have been found to play crucial roles in cancer biology. Retinoblastoma is a rare tumor that develops rapidly from a malignant tumor of immature cells in the retina known as photoreceptor progenitors. Our study aimed to explore the role of miR-146a in the pathology of retinoblastoma. Potential target gene of miR-146a was predicted by Targetscan. Reverse transcription quantitative polymerase chain reaction (RT-PCR) showed that miR-146a was downregulated and ventral nerve tumor antigen 1 (Neuro - oncological ventral antigen 1, NOVA1) was upregulated in retinoblastoma. Luciferase assay confirmed that miR-146a directly target NOVA1. MiR-146a knockdown and overexpression experiments were performed and found that miR-146a could regulate the expression of NOVA1. The miR-146a knockdown and overexpression experiments were conducted to investigate the biological function of miR-146a. MiR-146a was found inhibited the viability, proliferation and invasion of retinoblastoma cell by MTT, EdU, and transwell assays. Flow cytometry was performed for the apoptosis analysis and miR-146a increased the apoptosis of retinoblastoma cell was found. Above phenomenon can be rescued by overexpression of NOVA1. In conclusion, these results suggest that miR-146a acts as a tumor suppressor and can act as a potential therapeutic target for retinoblastoma in the future.

Keywords: NOVA1; apoptosis; invasion; miR-146a; proliferation; retinoblastoma.

MeSH terms

  • Apoptosis / genetics
  • Base Pairing
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neuro-Oncological Ventral Antigen
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Retinal Neoplasms / genetics*
  • Retinal Neoplasms / metabolism
  • Retinal Neoplasms / pathology
  • Retinoblastoma / genetics*
  • Retinoblastoma / metabolism
  • Retinoblastoma / pathology
  • Signal Transduction

Substances

  • MIRN146 microRNA, human
  • MicroRNAs
  • NOVA1 protein, human
  • Neuro-Oncological Ventral Antigen
  • RNA-Binding Proteins
  • Luciferases